Attempts have been made over the past several years to use antibodies in covalent combination with cytotoxic agents, thereby seeking to effect selective action on target cells and to prevent or at least to substantially diminish the otherwise relatively nonspecific effect of cytotoxic agents. A review of the use of antibody-linked cytotoxic agents is provided in Ghose et al., J. Natl. Cancer. Inst. 61, 657-676 (1978).
Although much effort has been directed to the use of antibodies for cell-directing purposes, especially in view of the now available monoclonal antibodies, the search continues to discover other viable cell-directing moieties. It is to compositions containing one such cell-directing moiety that the present invention is directed.
Transferrin is a circulating glycoprotein that acts as a carrier for iron and therefore provides a mechanism for delivering iron to the hematopoietic system. Transferrin introduces iron into cells via transferrin receptors present on the cell surfaces. The number of transferrin receptors on the cell surface is dependent upon cell type and is highly variable. In general, however, those cells that domonstrate high proliferation tend correspondingly to have great numbers of transferrin receptors. One general class of cells having large numbers of transferrin receptors is tumor cells and, in particular, leukemia cells.
It is on the above premise that the present invention is founded.